Imidazo-benzoxazinones, the preparation thereof and pharmaceutical compositions containing these compounds

Abstract

The invention relates to new imidazo-benzoxazinones of formula <IMAGE> (I) wherein the substituents are defined herein below, which compounds are useful in the treatment of cardiovascular disorders.

What is claimed is: 
     
       1. New imidazo-benzoxazinones of formula ##STR9## wherein R 1  is an alkyl group optionally substituted by a phenyl or pyridyl group, an alkyl group with 4 to 6 carbon atoms, a mercapto group optionally substituted by an alkyl group, a vinylene group which is substituted in the end position by a phenyl or pyridyl group, a phenyl group optionally substituted by a halogen atom or by a hydroxy, alkoxy, mercapto, alkylmercapto, alkylsulfinyl, alkylsulfonyl, cyano, amino or nitro group, whilst a hydroxyphenyl group may additionally be substituted by one or two alkyl groups each having 1 to 4 carbon atoms or an aminophenyl group may be substituted by one or two halogen atoms; a phenyl group disubstituted by halogen atoms, hydroxy, alkoxy, mercapto, alkylmercapto, alkylsulfinyl or alkylsulfonyl groups, the substituents of the phenyl nucleus being either identical or different, a 5-or 6-membered heteroaromatic ring bound via a carbon atom, and containing an oxygen, sulphur or nitrogen atom, two or three nitrogen atoms or one nitrogen atom and one oxygen or sulphur atom, to which one or two 1,4-butadienyl groups may additionally be bonded via two adjacent carbon atoms, whilst in the case of pyridine these may additionally be substituted by an amino, alkanoylamino or morpholino group or by two halogen atoms or by one halogen atom and an amino or morpholino group, or a 5- to 7-membered saturated imino, N-alkylimino or N-alkanoyl-imino-alkylene ring, bonded via a carbon atom, in which a methylene group in the 4-position may be replaced by an imino, alkylimino or alkanoylimino group or a --CH 2  CH 2  -- group may be replaced by an --NH--CO-- group, whilst the CO group of this --NH--CO group must be linked to the existing N-atom, and moreover all the above-mentioned heteroaromatic rings and saturated rings may be substituted by an alkyl group, R 2  is an hydrogen atom, an alkyl group with 1 to 6 carbon atoms optionally substituted from position 2 by a hydroxy or alkoxy group, or a phenylalkyl group,   R 3  and R 4 , which may be identical or different, are hydrogen atoms or alkyl, whilst the alkyl moiety of all the above-mentioned groups may contain from 1 to 3 carbon atoms unless otherwise stated,   the 3H-tautomers or nontoxic, phrrmaceutically acceptable acid addition salts thereof.   
     
     
       2. The imidazo-benzoxazinones of formula I as recited in claim 1, wherein R 1  is an alkyl group with 1 or 2 carbon atoms optionally substituted by a phenyl or pyridyl group; an alkyl group with 3 to 5 carbon atoms; a mercapto group optionally substituted by a methyl group; a vinylene group substituted in the end position by a phenyl or pyridyl group; a phenyl group optionally substituted by a hydroxy, methoxy, methylmercapto, methylsulfinyl, methylsulfonyl, cyano or nitro group; a dimethoxyphenyl, 3,5-di-tert.butyl-4-hydroxyphenyl, 4-amino-3,5-dihalo-phenyl, pyridyl, piperidinyl, morpholinopyridyl, quinolyl, furanyl, thienyl or pyrazinyl group,   R 2  is a hydrogen atom, a methyl, benzyl, ethyl, n-propyl, isopropyl, 2-hydroxyethyl or 2-methoxyethyl group,   R 3  and R 4 , which may be identical or different, are hydrogen atoms, methyl or ethyl groups,   the 3H-tautomers or nontoxic, pharmaceutically acceptable acid addition salts thereof.   
     
     
       3. The imidazo-benzoxazinones of formula I as recited in claim 1, wherein R 1  is an alkyl group with 1 to 3 carbon atoms or a pyridyl, pyrazinyl, furyl or thienyl group,   R 2  is a hydrogen atom or a methyl or ethyl group,   R 3  and R 4  each represent a methyl group,   the 3H-tautomers or nontoxic, pharmaceutically acceptable acid addition salts thereof.   
     
     
       4. 8,8-Dimethyl-2-(4-pyridyl)-8-hydro-(5H)-imidazo [5,4-g][3,1]benzoxazin-6-one, the 3H-tautomers or nontoxic, pharmaceutically acceptable acid addition salts thereof. 
     
     
       5. 5-Ethyl-8,8-dimethyl-2-(4-pyridyl)-8-hydro-(5H)-imidazo[5,4-g][3,1]benzoxazin-6-one, the 3H tautomers or nontoxic, pharmaceutically acceptable acid addition salts thereof. 
     
     
       6. A pharmaceutical composition of matter comprising a therapeutically effective amount of a compound as recited in claim 1 and a pharmaceutically acceptable carrier. 
     
     
       7. A method for treatment of chronic cardiac insufficiency in a warm-blooded animal which comprises administering to said animal a therapeutically effective amount of a compound as recited in claim 1. 
     
     
       8. A method for treatment of acute cardiac insufficiency in a warm-blooded animal which comprises administering to said animal a therapeutically effective amount of a compound as recited in claim 1. 
     
     
       9. A method for prevention of arterial thromboembolism in a warm-blooded animal which comprises administering to said animal a therapeutically effective amount of a compound as recited in claim 1. 
     
     
       10. A method for treatment of diseases of arterial occlusion in a warm-blooded animal which comprises administering to said animal a therapeutically effective amount of a compound as recited in claim 1.